Overview
As their name indicates, non-functioning pituitary adenomas (NFPAs), also called non-secretory adenomas, do not result in excess pituitary hormone production. As NFPAs do not produce any hormones they are usually slow to produce symptoms and tend to grow large before being discovered, creating pressure on the normal pituitary gland that results in hypopituitarism, and on the nearby critical structures such as the optic nerves and chiasm causing visual field defects.

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Non-functioning pituitary adenomas represent approximately 30% of all pituitary tumors and they are usually macroadenomas (more than 1 cm in diameter). Although prolactin-secreting adenomas, or prolactinomas, are the most common of all pituitary tumors in general, the most common macroadenomas are NFPAs.

Causes
Local growth of NFPAs exerts pressure on the pituitary gland leading to varying degrees of pituitary dysfunction. The pituitary cells that are most susceptible are the gonadotrophs, which are responsible for the production of sex hormones such as luteinizing hormone (LH) follicle-stimulating hormone (FSH) and testosterone followed by the thyrotrophs that produce the thyroid stimulating hormone (TSH), the somatotrophs that produce the growth hormone (GH), and the corticotrophs that produce adrenocorticotropic hormone(ACTH).

As the tumor expands beyond the confines of the sella turcica (the bony depression at the base of the skull which harbors the pituitary gland), neurological symptoms and signs begin to manifest. Headache, a common complaint, occurs as the expanding tumor stretches the sellar dura. Suprasellar growth and resultant optic nerve compression causes varying degrees of visual disturbance and visual field defects (mainly peripheral), and massive suprasellar growth may cause obstructive hydrocephalus and elevated intracranial pressure (ICP). Lateral growth into the cavernous sinuses (a pair of large venous sinuses on either sides of the pituitary gland that house many important cranial nerves) may cause diplopia and facial pain or numbness. Further lateral growth into the mesial temporal lobe may provoke epileptic seizures.

Pituitary failure results from destruction of the normal pituitary gland by the growing tumor and it may manifest itself in many ways based on which hormone or group of hormones are affected. Hypopituitarism can be partial or may lead to a complete deficiency of all pituitary hormones (panhypopituitarism).

Deficiency of sex hormones results in hypogonadism, which in men causes diminished libido and erectile dysfunction, and in females causes disturbance or complete cessation of the menstrual cycle i.e. amenorrhea, as well as diminished libido. Hypothyroidism can cause an array of symptoms including headache, weight gain, constipation, cold intolerance, depression, and diminished mental acuity.

The most common symptom of NFPAs, however, is gradual visual deterioration due to direct pressure by the adenoma on the optic nerves and chiasm, this may also be associated with eye muscle paralysis if the tumor has invaded the cavernous sinuses.

Most of non-functioning pituitary tumors are macroadenomas (over 1 cm in size) when finally diagnosed, the fact that they are non-secretory often delays the onset of symptoms till the tumor reaches a considerable size. Occasionally, they grow quite large and into the cavernous sinuses causing symptoms and signs related to cranial nerve(s) compression such as diplopia (double vision) and may obstruct the cerebrospinal fluid pathways resulting in increased intracranial pressure and hydrocephalus. Some patients with large pituitary tumors may have acute hemorrhage or infarction of the tumor (pituitary apoplexy) causing sudden onset of headache, visual loss, double vision, and/or pituitary failure, this condition is considered a surgical emergency requiring surgical decompression.

Diagnosis
A careful medical history and neurological examination focused on endocrinological findings is essential in all patients. Further evaluation is made by hormonal, radiological and neuropthalmological studies.

Hormonal evaluation is conducted by careful screening of the pituitary hormones in the blood to reveal any possible hypopituitarism. These blood tests evaluate baseline levels of different pituitary hormones such as TSH, ATCH, LH etc. Based on the results of the blood tests, additional hormonal studies may be required.

Radiological evaluation includes magnetic resonance imaging (MRI) of the pituitary with and without gadolinium (a contrast agent) for visualizing the pituitary tumor, determining its size, location, and appropriate treatment plan. Dynamic MRI of the pituitary gland, a technically new imaging tool, has also gained importance in the evaluation of pituitary adenomas due to its ability to delineate small microadenomas and differentiate them from the normal pituitary gland. In most instances, a computed tomography (CT) scan with and without contrast will also detect an adenoma but with lower accuracy than MRI and small tumors might be missed.

Neuro-ophthalmological assessment to obtain a baseline for vision and evaluate any existing visual problems, a major symptom of patients with NFPAs, is done through visual acuity testing, fundus examination (fundoscopy) and formal visual field testing (perimetry).

Treatment
Treatment options include observation, medical therapy, radiation therapy, and surgery. Observation is sometimes appropriate for patients with NFPAs, especially for smaller tumors that do not threaten vision or cause headaches or other symptoms, this decision must be taken carefully and the patient must be closely followed-up with periodic MRI scans and blood testing for hormonal levels. Observation may also be appropriate in older patients who suffer from other serious medical problems. For symptomatic pituitary adenomas, observation, as well as medical treatment, do not have a significant role as there are no medications that reliably slow or stop the growth of NFPAs. Medications such as dopamine agonists (bromocriptine) and somatostatin analogs (octreotide) have been tried but are mostly ineffective.

Radiation therapy is seldom used in the treatment of NFPAs and is mostly reserved for recurrent and residual cases or if surgery could not be tolerated by the patient due to other health problems.

Surgery for adenoma removal can yield excellent results as it effectively relieves the mass effect caused by the tumor such as the visual manifestations caused by pressure on the optic nerve(s).

Prognosis
For the majority of patients with symptomatic NFPAs, surgery for adenoma removal is the preferred and most effective modality of therapy. In most patients, tumor resection improves or reverses visual acuity and visual field deficits and other pressure manifestations such as headache. Hormonal function may gradually return to normal, and a complete cure is obtainable. Postoperatively, periodic MRIs and hormonal assessment should be carried out for the rest of the follow-up period.